Ageing research reviewsJan 12, 2025

Gut bacteria in Alzheimer's disease: Molecular pathways and possible treatments

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

Gut microbiota may play a crucial role in Alzheimer's disease pathogenesis and progression.

Dysbiosis of gut microbiota may compromise intestinal barrier integrity, allowing harmful molecules to enter the bloodstream and brain.
The production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites by gut microbiota could influence the risk of Alzheimer's disease.
The vagus nerve may facilitate communication between the gut and brain, impacting Alzheimer's disease.
While preclinical studies indicate potential benefits of targeting gut microbiota for Alzheimer's treatment, clinical evidence is limited and inconsistent.
There is a need for further research to clarify the exact molecular mechanisms linking gut microbiota to Alzheimer's disease.

Simplified

Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.

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Competing interests

Declaration of Competing Interest EE is the unique owner of 2E Science, a for-profit private scientific company. Neither EE nor 2E Science have any commercial interest or financial tie in relation with this article. GM served as a consultant for First Wave BioPharma, as a speaker for Takeda, Abbvie, Galapagos, and Pfizer, and filed a patent related to the treatment of inflammatory bowel diseases with Smad7 antisense oligonucleotides. BPI is an employee at Chiesi Farmaceutici. He is listed among the inventors of a number of Chiesi Farmaceutici’s patents of anti-Alzheimer drugs. SL, AM, FC, CI, PM, JP-F, MM-P, PC-E, SL-O, and AS-L declare that they have no conflict of interest.

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Gut bacteria in Alzheimer's disease: Molecular pathways and possible treatments

Abstract

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Competing interests

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